Unaccustomed muscular activity of even moderate intensity results in a certain amount of damage to contractile proteins and associated connective tissue. Eccentric exercise, in which muscles lengthen as they develop tension, is a natural part of most forms of exercise and is a particularly potent inducer of damage. An inflammatory response is associated with this muscle damage which might contribute to catabolic processes and may mediate muscle protein turn over responsible for repair. We propose to use eccentric exercise to examine age-related differences in the inflammatory response associated with muscle damage. The inflammatory response will be measured in blood and in skeletal muscle. Circulating immune complexes, functional complement activity, interleukin-l (IL-l), humor necrosis factor (TNF), and humoral cytotoxic factors will be measured. In muscle, HLA class I antigens, IL-l, and TNF concentrations and receptor numbers will be determined and the immunohistological characterization of invading leukocytes will be performed. The influence of the non- steroidal anti-inflammatory drug indomethacin, and the influence of dietary omega-3 fatty acid supplementation on all of these parameters will be assessed as well. By examining the systemic and intramuscular processes involved in damaging exercise, the mechanisms which may be critically important effectors of repair and peripheral training in young and old subjects will be characterized for the first time. This study will bring together novel methods to examine responses to muscle damage and differentiate between the young and the old. These data will be important for the athlete, but perhaps more important for the millions of old and young people beginning a program of increased physical activity. Moreover, the eccentric exercise protocol may prove to be a safe and controlled alternative experimental model for studying inflammation the elderly.